D. Abstract (Animal Models & Phenotyping Core) During the past 10 years (Y1-5 and Y6-10 of funding), the mandate of the Animal Models and Phenotyping Core (AMPC) was to make high quality transgenic and gene knockout mouse production and metabolic and behavioral phenotyping readily accessible, both technically and financially, to NORC members. The Animal Models and Phenotyping Core (AMPC) is comprised of two interactive components: the Animal Models Subcore and the Energy Metabolism and Behavioral Subcore. THE AMPC provides services that combined controlled manipulation of gene expression in mice with state-of-the-art in vivo metabolic phenotyping and detailed behavioral analysis. Over the past two funding cycles (Y1-5, Y6-10), the APMC has been a key component of the overall mission of the Pennington NORC to stimulate new and innovative research related to nutrition and obesity. The aims of the core are as follows: Aim 1: To utilize transgenic and gene targeting techniques to generate mouse models that mimic human disease states, such as obesity and insulin resistance, when exposed to an obeseogenic environment (sedentary lifestyle and high caloric diets). Aim 2: To conduct detailed in vivo metabolic phenotyping to assess measures of physiologic function such as, energy expenditure, fat accumulation, food intake, and metabolic flexibility. Aim 3: Conduct in vivo experiments for detailed analysis of animal behavior so as to support NORC members and the Pilot and Feasibility Program. Aim 4: Pursue new methods and experimental paradigms based on observations from NORC members and Pilot and Feasibility experiments. The above Aims will be performed using a combination of genetic and other in vivo approaches. Experiments in which the genetic constitution can be changed to study the role of specific genes on obesity and diabetes cannot be performed in humans. These studies will identify mechanisms that act on the progression of metabolic dysfunction (i.e., insulin resistance, ectopic fat deposition, metabolic inflexibility, pancreatic dysfunction, etc) by using rodent models that develop obesity and insulin resistance through direct genetic manipulation or exposure to high fat diets. Thus, through rigorous in vivo metabolic phenotyping in conjunction with detailed mechanistic analysis of relevant tissues by NORC investigators, the AMPC helps all NORC projects address the critical unanswered question of how an obesogenic environment affects normal metabolism at the whole body level.